Study of Low-grade Systemic Inflammation in Adult Patients With Phenylketonuria

NCT ID: NCT04879277

Last Updated: 2021-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-26

Study Completion Date

2021-08-25

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Patient suffering from phenylketonuria have chronic hyperphenylalaninemia. Hyperphenylalaninemia is known to be toxic to central nervous system and cardiovascular system in particular through oxydative stress.

In this context, research of low grade systemic inflammation through cytokine assay appears legitimate.

The primary outcome of this study is to describe inflammation profile of patients with phenylketonuria.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Phenylketonuria (PKU) is a metabolic hereditary disease due to lack of activity of phenylalanine hydroxylase. This lack of activity whom origin is genetic, results in chronic hyperphenylalaninemia, toxic to central nervous system and cardiovascular system. Without treatment, PKU is responsible for mental retardation in children.

PKU is subject to systematic screening at birth and if diagnosis is confirmed a specific diet controlled in phenylalanine is prescribed for infant. This diet allows a neurodevelopment as closed as healthy infant. Despite this diet, neurological and systemic complications are more often reported at adult age. It is therefore recommended to follow patient regularly in order to search for those complications.

In a PKU murine model, it has been shown (cf references) that a low grade systematic inflammation exists and was reversible after dietetic treatment using glycomacropeptide (through a probiotic effect of this protein naturally phenylalanine free). Existence of this low grade systematic inflammation, evaluated by plasmatic cytokine screening (TNF alpha IL2, IL6, IL10, IFNgamma, IL1Alpha, IL1Beta and protein C reactive) has not been proven in humans to date.

Primary outcome of this study is to characterize this low grade systemic inflammation profile in patient with PKU.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Phenylketonuria

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Low grade inflammation Cardiovascular Phenylketonuria

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

One group of healthy subject and one group of patient with phenylketonuria. Primary objective is to compare inflammation profile between the two groups through cytokine assay.
Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Healthy subject

The intervention, specific to the study, is to take blood samples on patients healthy volunteers.

Healthy subject will be paired to patient with phenylketonuria according to body mass index and sex.

Group Type OTHER

Blood samples

Intervention Type BIOLOGICAL

Plasmatic cytokine and plasmatic CRP assay will be realised using luminex in both arms. IL2, IL10,INF gamma, IL, IL6, ILB, TNF alpha will be analysed.

Patient with phenylketonuria

The intervention, specific to the study, is to take blood samples on patients with phenylketonuria

Group Type OTHER

Blood samples

Intervention Type BIOLOGICAL

Plasmatic cytokine and plasmatic CRP assay will be realised using luminex in both arms. IL2, IL10,INF gamma, IL, IL6, ILB, TNF alpha will be analysed.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Blood samples

Plasmatic cytokine and plasmatic CRP assay will be realised using luminex in both arms. IL2, IL10,INF gamma, IL, IL6, ILB, TNF alpha will be analysed.

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Plasmatic Cytokine and plasmatic CRP assay

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Age \>/= 18 years old
* Phenylketonuria diagnosis
* Fasting condition
* Registered with a social security system
* Patient consent


* Age \>/= 18 years old
* No metabolic condition
* Fasting condition
* Paired to patient with phenylketonuria already included according to age, sex and BMI class
* Registered with a social security system
* Volunteer consent

Exclusion Criteria

* Pregnant and lactating women
* Subject to legal protection measures.
* Chronic or acute inflammatory disease
* Fever on inclusion
* Undergoing anti inflammatory treatment
* Surgery in the previous months
* Diabetes
* Included in other therapeutic trial
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

François MAILLOT, MD-PhD

Role: STUDY_DIRECTOR

University Hospital, Tours

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Clinical investigation center, University Hospital, Tours

Tours, , France

Site Status

Internal Medicine Service, University Hospital, Tours

Tours, , France

Site Status

Countries

Review the countries where the study has at least one active or historical site.

France

References

Explore related publications, articles, or registry entries linked to this study.

Solverson P, Murali SG, Brinkman AS, Nelson DW, Clayton MK, Yen CL, Ney DM. Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria. Am J Physiol Endocrinol Metab. 2012 Apr 1;302(7):E885-95. doi: 10.1152/ajpendo.00647.2011. Epub 2012 Jan 31.

Reference Type BACKGROUND
PMID: 22297302 (View on PubMed)

van Spronsen FJ, van Wegberg AM, Ahring K, Belanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, Gizewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, Trefz FK, van Rijn M, Walter JH, MacDonald A. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol. 2017 Sep;5(9):743-756. doi: 10.1016/S2213-8587(16)30320-5. Epub 2017 Jan 10.

Reference Type BACKGROUND
PMID: 28082082 (View on PubMed)

Boulet L, Besson G, Van Noolen L, Faure P; ECOPHEN Study Group; Maillot F, Corne C. Tryptophan metabolism in phenylketonuria: A French adult cohort study. J Inherit Metab Dis. 2020 Sep;43(5):944-951. doi: 10.1002/jimd.12250. Epub 2020 Jun 4.

Reference Type BACKGROUND
PMID: 32392388 (View on PubMed)

Stroup BM, Nair N, Murali SG, Broniowska K, Rohr F, Levy HL, Ney DM. Metabolomic Markers of Essential Fatty Acids, Carnitine, and Cholesterol Metabolism in Adults and Adolescents with Phenylketonuria. J Nutr. 2018 Feb 1;148(2):194-201. doi: 10.1093/jn/nxx039.

Reference Type BACKGROUND
PMID: 29490096 (View on PubMed)

Matalon R, Surendran S, McDonald JD, Okorodudu AO, Tyring SK, Michals-Matalon K, Harris P. Abnormal expression of genes associated with development and inflammation in the heart of mouse maternal phenylketonuria offspring. Int J Immunopathol Pharmacol. 2005 Jul-Sep;18(3):557-65. doi: 10.1177/039463200501800316.

Reference Type BACKGROUND
PMID: 16164837 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2021-A01035-36

Identifier Type: OTHER

Identifier Source: secondary_id

DR210098

Identifier Type: -

Identifier Source: org_study_id